The goal of the proposed research is to define the first synthetic route toward 6-hydroxypunctaporonin E, a polycyclic natural product. 6-Hydroxypunctaporonin E was isolated from the fungicolous fungi Pestalotiopsis disseminata, collected in the state of Georgia, and was shown to have antibiotic properties inhibiting the growth of Bacillus subtilis and Staphylococcus aureas.[1] The proposed synthetic route includes an unusual example of the Diels-Alder reaction between a vinylcyclobutene and a dihydrofuranone. Included with the synthetic goal are the design of a novel chiral Lewis acid for Diels-Alder chemistry, and the study of a 6-hydroxypunctaporon E conjugate. PUBLIC HEALTH RELEVANCE: The development of broadly applicable antibiotic medicines is one of mankind's noteworthy accomplishments of the last century. Unfortunately, bacteria have begun to develop resistance to common medications used in the treatment of bacterial infections. As a result there is a continued need for research into the synthesis and biological evaluation of new compounds with antibiotic properties, to better understand their potential as new antibiotics of the future.